title: Herbacetin, a constituent of ephedrae herba, suppresses the HGF-induced motility of human breast cancer MDA-MB-231 cells by inhibiting c-Met and Akt phosphorylation.
abstract: Ephedrae herba suppresses hepatocyte growth factor-induced cancer cell motility by inhibiting tyrosine phosphorylation of the hepatocyte growth factor receptor, c-Met, and the PI3K/Akt pathway. Moreover, Ephedrae herba directly inhibits the tyrosine-kinase activity of c-Met. Ephedrine-type alkaloids, which are the active component of Ephedrae herba, do not affect hepatocyte growth factor-c-Met-Akt signalling, prompting us to study other active molecules in the herb. We recently discovered herbacetin glycosides and found that their aglycon, herbacetin, inhibits hepatocyte growth factor-c-Met-Akt signalling. This study revealed a novel biological activity of herbacetin. Herbacetin suppressed hepatocyte growth factor-induced motility in human breast cancer MDA-MB-231 cells by inhibiting c-Met and Akt phosphorylation and directly inhibiting c-Met tyrosine kinase activity. The effects of herbacetin were compared to those of kaempferol, apigenin, and isoscutellarein, all of which have similar structures. Herbacetin inhibition of hepatocyte growth factor-induced motility was the strongest of those for the tested flavonols, and only herbacetin inhibited the hepatocyte growth factor-induced phosphorylation of c-Met. These data suggest that herbacetin is a novel Met inhibitor with a potential utility in cancer therapeutics.
authors.affiliation: Department of Clinical Research, Oriental Medicine Research Center of Kitasato University, Tokyo, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Hyuga
authors.forename: Masashi
authors.initials: M
authors.lastname: Hyuga
authors.forename: Morio
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Amakura
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Goda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hanawa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; C581534:herbacetin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt